Clinical presentation. Hyperprolactinemia—the most common hypothalamic-pituitary disturbance—usually presents with clinical features of gonadal dysfunction (Table 1).8 Symptoms and signs related to a brain mass—headache, visual field disturbances, ophthalmoplegia, and reduced visual acuity—may predominate with a large pituitary tumor. The patient may first present to a primary care physician or to a clinical specialist, such as a gynecologist, neurologist, ophthalmologist, pediatrician, psychiatrist, or urologist.
Thirty to 80% of women with hyperprolactinemia develop galactorrhea,9 although some women with galactorrhea have normal prolactin levels. Men with hyperprolactinemia usually have gonadal dysfunction, which unfortunately is often attributed to “psychogenic” causes. Particularly in men, prolactin is implicated in the control of libido.
Causes. Hyperprolactinemia may be caused by any process that inhibits dopamine synthesis, the neurotransmitter’s transport to the anterior pituitary gland, or its action at the lactotrope dopamine receptors ( Table 2).9 In this article, we will limit our discussion to antipsychotic drugs. have long-term effects on bone density. Trabecular bone mass
Estrogen and prolactin. During pregnancy, the rise in estrogen levels probably stimulates an increase in prolactin. Increased prolactin levels are also found in women taking estrogen-containing oral contraceptives, although this effect is very small with low-estrogen formulations.
Table 2
CAUSES OF PATHOLOGIC HYPERPROLACTINEMIA
| Hypothalamic disease | Tumor, infiltrative disease, pseudotumor cerebri, cranial radiation |
| Pituitary disease | Prolactinoma, acromegaly, Cushing’s disease, glycoprotein-producing tumor, other tumors, pituitary stalk section, empty sella, infiltrative disease |
| Medications | Antipsychotics, dopamine receptor blockers, antidepressants, antihypertensives, estrogens, opiates, cimetidine |
| Others | Primary hypothyroidism, chronic renal failure, cirrhosis, neurogenic and idiopathic causes |
| Source: Adapted and reprinted from Vance ML, Thorner MO. Prolactin: hyperprolactinemic syndromes and management. In: DeGroot LJ, Besser M, Burger HG, et al (eds). Endocrinology. Philadelphia: W.B. Saunders, 1995:394-405. Copyright 1995, with permission from Elsevier Science. | |
Functions of the pituitary lactotrophs regulated by estrogen include prolactin gene expression, release, storage, and cellular expression.2 Estradiol inhibition of dopamine synthesis in the tuberoinfundibular dopaminergic neurons may contribute to some gender differences in neurocognitive function and to psychiatric conditions’ clinical features.
Hyperprolactinemia and bone density. Besides causing galactorrhea and sexual dysfunction, hyperprolactinemia may has been found to be reduced in young women with amenorrhea secondary to hyperprolactinemia. This trabecular osteopenia is reversible—spinal bone density decreases progressively without treatment and improves when hyperprolactinemia is treated. Menstrual function appears to best predict risk of progressive spinal osteopenia in women with hyperprolactinemia. Estradiol level is a stronger predictor of clinical course than is the prolactin level.10
Antipsychotic drugs and hyperprolactinemia
Among the four principal dopamine pathways in the brain, the tuberoinfundibular pathway is a system of short axons at the base of the hypothalamus that releases dopamine into the portal veins of the pituitary gland. Terminals in the median eminence of the hypothalamus release dopamine that travels down the pituitary stalk in the portal veins.
Typical antipsychotics block dopamine receptors both in the striatum and in the hypothalamus.11 This finding suggests that the older drugs lack specificity of dopamine blockade. Prolactin elevations in patients treated with older antipsychotics may be associated with sexual dysfunction—a common cause of drug noncompliance, particularly in men.12
Antipsychotics and sexual side effects. Patients taking antipsy-chotics often complain—spontaneously or after focused questioning—of sexual side effects caused by drug-induced hyperprolactinemia. Assessing antipsychotic-induced sexual dysfunction may be confounded by the psychoses being treated, patient compliance, and sexuality’s complexities. Antipsychotics are generally believed to reduce desire, cause orgasmic dysfunction, and lead to difficulties during sexual performance.8
Atypical antipsychotics
A recent study designed to assess the effect of three atypical antipsychotics on serum prolactin levels enrolled 18 men with schizophrenia (mean age 32) taking clozapine, 300 to 400 mg/d; risperidone, 1 to 3 mg/d; or olanzapine, 10 to 20 mg/d, for at least 8 weeks.13 The study participants were instructed not to take their antipsychotics the night before the study. Baseline prolactin levels were measured in the morning, the men took the full daily dose of their medications, and prolactin levels were measured every 60 minutes over the next 8 hours and again at 24 hours.
Mean baseline prolactin values of clozapine (9 ng/ml, SD=5) and olanzapine (9 ng/ml, SD=5) were in the normal range (<20 ng/ml), compared with those of risperidone (27 ng/ml, SD=14). Three of the six patients taking risperidone had hyperprolactinemia at baseline. Prolactin values doubled within 6 hours of administration of all three medications. There was no comparable increase in prolactin levels in five control subjects not taking antipsychotics.
The authors concluded that these atypical antipsychotics raise prolactin levels but more transiently than typical antipsychotics. They suggested that the differences among the three drugs may be attributed to each drug’s binding properties to pituitary dopamine D2 receptors. A similar study in four patients with first-episode schizophrenia found serum prolactin levels increased from <10 ng/ml at baseline to peak levels of 80 to 120 ng/ml within 60 to 90 minutes after patients took a full daily dose of quetiapine, 700 to 800 mg/d.14